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Biomedical subjects

A C van Houwelingen

Publications and source records attributed to A C van Houwelingen.

At least 19 recordsLinked to original sources

Determinants of neonatal IgE level: parity, maternal age, birth season and perinatal essential fatty acid status in infants of atopic mothers.

OBJECTIVE: The hygiene hypothesis suggests that the protective 'siblings effect' against atopic diseases such as atopic dermatitis, allergic asthma and hay fever is a result of recurrent infections during early childhood. A recent study and review have indicated that this protective effect may already arise in utero. Lower n-3 essential fatty acid (EFA) status is associated with increased parity, and EFA status has also been related to atopy. The present study confirms the negative association between parity and neonatal immunoglobulin E (IgE) levels and further unravel the role of perinatal EFA status. METHODOLOGY: In a prospective cohort study in 184 atopic mothers and their neonates, we simultaneously measured serum total IgE and EFA levels in plasma phospholipids, both in the mother at 34-36 weeks of gestation and in the neonate at the age of 1 week. Linear regression analysis was used to estimate the effect of parity on maternal and neonatal IgE and EFA status, and the independent effects of parity and EFA status on IgE, controlling for confounding factors such as maternal age and birth season. RESULTS: Parity was associated with lower neonatal IgE level (P < 0.01), as well as with lower docosahexanoic acid (DHA, 22:6n-3) status of the mother (P = 0.01) but not of the neonate (P > 0.69). In the multivariate analysis, higher parity, higher maternal IgE, lower maternal age and birth in the first 3 months of the year were independently associated with neonatal IgE level. No association was detected between maternal or neonatal EFA status and neonatal IgE. CONCLUSIONS: As neonatal total serum IgE is predictive of later atopy, our results support the hypothesis that the sibling effect in atopy is already being programmed in utero. Our data also confirm earlier findings that DHA status is lower in multiparous women, but this did not confound the relation between parity and neonatal IgE.

Fatty Acids, Essential↗

Changes in the maternal essential fatty acid profile during early pregnancy and the relation of the profile to diet.

BACKGROUND: Although the pattern of the essential fatty acids (EFAs) changes considerably from week 10 of pregnancy to term, no information is available on changes in EFA concentrations in the early stages of pregnancy. OBJECTIVE: The main objectives were to assess the EFA status, particularly that of 22:6n-3, in women during the first 10 wk of pregnancy and to investigate the relation of EFA status to dietary EFA intake during this period. DESIGN: Healthy women (n = 24) planning to become pregnant were recruited. The fatty acid composition of plasma and erythrocyte phospholipids was determined before and at weeks 4, 6, 8, and 10 of pregnancy. Food intake was assessed at entry into the study and at week 10 of pregnancy by using food-frequency questionnaires. RESULTS: A small but nonsignificant increase in dietary intake of 22:6n-3 was found. The plasma phospholipid content of 22:6n-3 (% by wt) increased continuously during the first 10 wk of pregnancy. At week 10 of pregnancy, the plasma percentages of 16:0, 20:3n-6, and 20:4n-6 had increased significantly, whereas the percentages of the 18-24-carbon saturated fatty acids, 18:2n-6, and the ratio of n-6 to n-3 fatty acids had dropped significantly. The composition of erythrocyte phospholipids showed changes similar to those observed in plasma. CONCLUSIONS: Maternal plasma and erythrocyte phospholipid 22:6n-3 concentrations start to increase in very early pregnancy, which cannot be explained by changes in dietary intake alone. This rise probably represents early maternal adaptations to meet the requirements of highly proliferating and differentiating tissues at this stage of fetal development.

Adult↗

Evaluation of the relation between n-3 and n-6 fatty acid status and parity in nonpregnant women from the Netherlands.

BACKGROUND: We previously observed an inverse relation between parity and docosahexaenoic acid (DHA) status in pregnant women in the Netherlands. This implies that maternal DHA status may not fully normalize after a mature pregnancy. OBJECTIVE: The objective was to investigate the relation between the essential fatty acid status (in particular the DHA status) of nonpregnant women and the number of completed pregnancies and whether the number of previous pregnancies is associated with a lower DHA status in women from the Netherlands. DESIGN: This was a cross-sectional study of 129 healthy nonpregnant women who completed 0, 1, 2, 3, or 4 mature, uncomplicated, singleton pregnancies. RESULTS: The relative amount of DHA in the plasma phospholipids of nulliparous women and of mothers who completed 1-4 pregnancies (duration since last pregnancy: 3.9 +/- 2.4 y) was not significantly different; a significant correlation between parity and the percentage of DHA in the phospholipids was not observed either. The percentage of DHA in the phospholipids of erythrocytes of mothers was significantly lower than the percentage in the erythrocytes of the nulliparas (P = 0.013), but no significant correlation between the percentage of DHA in the phospholipids of erythrocytes and parity was found. The time interval between the different pregnancies did not influence maternal DHA status. CONCLUSIONS: No relation was found between DHA status and parity in the nonpregnant Dutch women whose last pregnancy was completed > or = 1 y previously. Maternal DHA status, as reflected in plasma and erythrocyte phospholipids, probably normalized within 1 y after the last partus. Whether this is true for other tissues remains to be determined.

Adult↗

Comparison of the peripartum and postpartum phospholipid polyunsaturated fatty acid profiles of lactating and nonlactating women.

BACKGROUND: Pregnancy is associated with increased absolute amounts of docosahexaenoic acid (DHA; 22:6n-3) in plasma phospholipids. Expressed as a proportion of total fatty acids, DHA declines slightly in late pregnancy but little information is available on the normalization of DHA postpartum, which may be different in lactating and nonlactating women. OBJECTIVE: The aim was to investigate maternal plasma and erythrocyte long-chain polyunsaturated fatty acids (long-chain polyenes; LCPs) postpartum, particularly DHA, in relation to lactation and dietary LCP intake. DESIGN: Healthy pregnant women who intended to breast-feed or exclusively bottle-feed their infants were studied at 36-37 wk of pregnancy. Blood samples were collected at entry, after parturition on days 2 and 5, and 1, 2, 4, 8, 16, 32, and 64 wk postpartum. Fatty acid profiles were analyzed in plasma and erythrocyte phospholipids. Dietary intakes were assessed 4 and 32 wk postpartum with a validated food-frequency questionnaire. RESULTS: After delivery, the percentages of plasma linoleic, arachidonic, eicosapentaenoic, and docosapentaenoic acids increased over time, whereas the percentage of docosapentaenoic acid decreased; the patterns of change did not differ significantly between the lactating and nonlactating groups. The percentage of DHA in plasma and erythrocyte phospholipid fatty acids declined significantly in the 2 groups, more so in the lactating women, and was enhanced when the lactation period was extended. Despite the apparent higher dietary intake of essential fatty acids in the lactating group at week 4, it was not significantly different from that of the nonlactating group. CONCLUSION: Normalization of maternal plasma and erythrocyte phospholipid n-3 LCPs differs significantly between lactating and nonlactating women postpartum but that of n-6 LCPs does not.

Adult↗

The effect of supplementation with docosahexaenoic and arachidonic acid derived from single cell oils on plasma and erythrocyte fatty acids of pregnant women in the second trimester.

This study was performed to investigate whether supplementation of docosahexaenoic acid (DHA) and arachidonic acid (AA) to pregnant women would enhance their DHA levels, both in plasma and in erythrocyte phospholipids, without reducing the content of n-6 long-chain ployenes (LCP) usually seen when DHA is supplemented alone. Healthy pregnant women, in the second trimester, were randomly assigned to either the control group (n=12) or the intervention group (n=12). The control group received no supplements and the intervention group received daily during 4 weeks encapsulated algae-derived DHA oil (0.57 g DHA/day) and fungal-derived AA oil (0.26 g AA/day). The fatty acid compositions of plasma and erythrocyte phospholipids were determined in weekly-collected blood samples. DHA and n-6 LCP levels of the control group were unchanged after 4 weeks. Compared to the control group, DHA levels in plasma an erythrocytes of the intervention group increased significantly. No significant reductions were found in the levels of AA and total n-6 LCP. The supplement proved to be effective in increasing the DHA levels in both plasma and erythrocyte without a concomitant decline of the n-6 LCP.

Adult↗

Long-chain polyunsaturated fatty acids, pregnancy, and pregnancy outcome.

During pregnancy, essential long-chain polyunsaturated fatty acids (LCPUFAs) play important roles as precursors of prostaglandins and as structural elements of cell membranes. Throughout gestation, accretion of maternal, placental, and fetal tissue occurs and consequently the LCPUFA requirements of pregnant women and their developing fetuses are high. This is particularly true for docosahexaenoic acid (DHA; 22:6n-3). The ratio of DHA to its status marker, docosapentaenoic acid (22:5n-6), in maternal plasma phospholipids decreases significantly during pregnancy. This suggests that pregnancy is associated with maternal difficulty in coping with the high demand for DHA. The DHA status of newborn multiplets is significantly lower than that of singletons; the same is true for infants of multigravidas as compared with those of primigravidas and for preterm compared with term neonates. Because the LCPUFA status at birth seems to have a long-term effect, the fetus should receive an adequate supply of LCPUFAs. Data from an international comparative study indicated that, especially for n-3 LCPUFAs, the fetus is dependent on maternal fatty acid intake; maternal supplementation with LCPUFAs, their precursors, or both increased LCPUFA concentrations in maternal and umbilical plasma phospholipids. However, significant competition between the 2 LCPUFA families was observed, which implies that effective supplementation requires a mixture of n-6 and n-3 fatty acids. Further research is needed to determine whether higher LCPUFA concentrations in plasma phospholipid will have functional benefits for mothers and children.

Adult↗

Nutritional supplementation with N-3 fatty acids and antioxidants in patients with Crohn's disease in remission: effects on antioxidant status and fatty acid profile.

In patients with Crohn's disease (CD), malnutrition is frequently observed and is generally accepted to be an important issue. The aim of this study was to investigate the effects of 3 months of supplementation with a liquid formula containing either antioxidants (AO) or n-3 fatty acids plus AO on the antioxidant status and fatty acid profile of plasma phospholipids and adipose tissue, respectively, in patients with long-standing CD currently in remission. In a randomized, double-blind placebo-controlled study, CD patients received either placebo, AO, or n-3 fatty acids plus AO for 3 months in addition to their regular diet. In all, 25/37 CD patients completed the study. AO status was assessed by blood biochemical parameters. A statistical per-protocol analysis was performed. Serum concentrations of selenium, vitamin C, and vitamin E, the activity of superoxide dismutase and total antioxidant status were significantly (p < 0.05) increased after AO supplementation. Furthermore, compared with controls, serum concentrations of beta-carotene, selenium, and vitamin C and the activity of glutathione peroxidase (GPx) were significantly (p < 0.05) lower before supplementation; however, after AO supplementation these levels were not significantly different from controls (except for GPx). N-3 fatty acids plus AO supplementation significantly (p < 0.05) decreased the proportion of arachidonic acid, and increased the proportion of eicosapentanoic acid and docosahexanoic acid in both plasma phospholipids and adipose tissue. Supplementation with antioxidants improved antioxidant status in patients with CD in remission. In addition, supplementation with n-3 fatty acids plus antioxidants significantly changed the eicosanoid precursor profile, which may lead to the production of eicosanoids with attenuated proinflammatory activity. This study indicates that an immunomodulating formula containing n-3 fatty acids and/or AO may have the potential to play a role in the treatment of CD.

Adult↗

Effects of pregnancy-induced hypertension on the essential fatty acid statuses of Ecuadorian and Dutch women.

OBJECTIVE: Among white Dutch women pregnancy-induced hypertension was shown to be associated with elevated levels of the long-chain polyenes of 18:2n-6 and 18:3n-3 in combination with reduced levels of those parent essential fatty acids. This observation suggested an enhanced desaturation and elongation of the parent fatty acids. This study was performed to investigate whether this phenomenon also occurs under completely different nutritional and geographic conditions. STUDY DESIGN: Plasma fatty acids of primiparous Mestizo Ecuadorian women with uncomplicated pregnancies and with pregnancy-induced hypertension were assessed at delivery and compared with similar data from white Dutch women. Neonatal values, as determined in umbilical plasma and umbilical vessel walls, were also compared. RESULTS: In contrast to the pattern seen among white mothers, pregnancy-induced hypertension did not increase the long-chain polyene status of Mestizo mothers. Despite the absence of this compensatory mechanism, long-chain polyene status was not compromised in Mestizo neonates born after pregnancy-induced hypertension. CONCLUSION: Additional mechanisms may be active in maintaining the long-chain polyene status of neonates born after pregnancy-induced hypertension.

Adult↗

Early nutrition, essential fatty acid status and visual acuity of term infants at 7 months of age.

OBJECTIVE: In term infants the relationship between visual acuity and dietary fatty acid composition is not consistent, possibly due to confounders, which were mostly neglected in the studies concerned. In the current study, therefore, the influence of the essential fatty acid status and potential confounders on the visual acuity was investigated. DESIGN: The essential fatty acid status was determined at 7 months of age in red blood cell and plasma phospholipids of breastfed and formula-fed infants, born at term. Visual acuity was measured with Teller Acuity Cards. Information about potential confounding factors was obtained during an interview and with a retrospective questionnaire. RESULTS: This study, like others, showed that the concentrations of docosahexaenoic acid (DHA, 22:6n-3) are lower in plasma and red blood cell phospolipids of formula-fed infants compared to that of breastfed infants. However, no differences in visual acuity could be found between the two groups. Moreover, no significant relationship was found between the amounts of docosahexaenoic acid in plasma and red blood cell phospholipids and the visual acuity. Although dummy (pacifier) use showed a significant positive correlation with visual acuity, it did not influence the relationship between the essential fatty acids in the infant diet and visual acuity. There was also no confounding influence of smoking habits and alcohol use during pregnancy, socioeconomic background and other potential confounders. CONCLUSIONS: At 7 months of age no influence of fatty acid status, infant diet or potential confounders on visual acuity was found.

Breast Feeding↗

A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations.

BACKGROUND: Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory. OBJECTIVE: To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease. DESIGN: In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L. RESULTS: Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change. CONCLUSION: The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations.

Adenosine Triphosphate↗

Maternal and neonatal plasma antioxidant levels in normal pregnancy, and the relationship with fatty acid unsaturation.

During pregnancy, maternal plasma concentrations of the peroxidation-susceptible polyunsaturated fatty acids (polyenes) increase. In addition, the proportion of polyenes is higher in neonatal plasma than in maternal plasma. To study whether these increased amounts of polyenes affect antioxidant levels, we measured lipid-soluble antioxidants in maternal and neonatal plasmas obtained during thirty-five normal pregnancies. These values were then related to the degree of phospholipid-fatty acid unsaturation. Maternal plasma levels of tocopherols and lutein increased during pregnancy, as assessed at 14, 22, and 32 weeks of gestation. However beta-carotene levels decreased, and levels of other carotenoids remained unchanged. Retinol levels were only decreased at 32 weeks of gestation. The value for alpha-tocopherol: phospholipid-polyene unsaturation index (UI) also increased during pregnancy, despite the observed increase in UI. Corresponding ratios for several carotenoids and retinol, however, decreased during pregnancy. After delivery, maternal plasma levels of delta-tocopherol and beta + gamma-tocopherol, as well as beta + gamma-tocopherol: UI values, were lower than values at 32 weeks of gestation. Umbilical-cord plasma antioxidant levels and antioxidant: UI values, except retinol: UI, were significantly lower than maternal values. Significant and consistent cord v. maternal correlations were observed for plasma levels of beta + gamma-tocopherol, lutein and beta-carotene, but not for delta-tocopherol, alpha-tocopherol, lycopene, alpha-carotene, and retinol. In conclusion, although during pregnancy maternal plasma tocopherol levels increased concurrently with, or more than, fatty acid unsaturation in plasma phospholipids, the decrease in carotenoid: UI values during gestation, the decrease in maternal plasma levels of delta-tocopherol and beta + gamma-tocopherol after delivery, and the low neonatal antioxidant levels merit further investigation.

Antioxidants↗

Pregnancy-induced hypertension: maternal and neonatal plasma lipid-soluble antioxidant levels and its relationship with fatty acid unsaturation.

OBJECTIVE: Our purpose was to investigate whether plasma lipid-soluble antioxidant levels during the third trimester of pregnancy and immediately after birth are altered in women with pregnancy-induced hypertension. DESIGN: Nested case-control study of women with pregnancy-induced hypertension. SUBJECTS: A group of 23 women with (mild) pregnancy-induced hypertension and their neonates, were compared with 23 matched controls with uncomplicated pregnancies. METHODS: Concentrations of vitamin E isomers, several carotenoids, and retinol were determined by HPLC in venous plasma which had been stored for 2-5 y. Antioxidant levels were adjusted for the degree of fatty acid unsaturation in plasma phospholipids as analysed 2-5 y before. RESULTS: In the third trimester of pregnancy, lipid-soluble antioxidant levels were similar in women with pregnancy-induced hypertension and controls. From the third trimester to postpartum, mean (+/- s.e.m.) beta + gamma-tocopherol levels decreased by 0.38 +/- 0.17 mumol/l or 5% (P = 0.038) in the control group. In the pregnancy-induced hypertension group, however, plasma levels of most antioxidants decreased from the third trimester to postpartum, but only the decreases in plasma levels of beta + gamma-tocopherol of 1.08 +/- 0.27 mumol/l or 26% (P = 0.042), of alpha-tocopherol of 2.51 +/- 1.58 mumol/l or 6% (P = 0.024), and of lutein of 0.13 +/- 0.04 mumol/l or 15% (P = 0.013) reached statistical significance as compared with the changes in the control group. At the same time, the polyunsaturated fatty acid unsaturation index of plasma phospholipids (UI) decreased in the pregnancy-induced hypertension group as well. Consequently, antioxidant levels, adjusted for UI, changed similarly in both groups. Umbilical vein plasma antioxidant levels were also similar after complicated and uncomplicated pregnancies. CONCLUSION: Plasma lipid-soluble antioxidant levels in mother and child are affected by mild pregnancy-induced hypertension, but this effect disappears after adjustment for fatty acid unsaturation.

Antioxidants↗

Fetal growth is associated positively with maternal intake of riboflavin and negatively with maternal intake of linoleic acid.

OBJECTIVE: To examine whether dietary factors in pregnancy are related to fetal growth. DESIGN: Prospective longitudinal study during pregnancy; midway through gestation a dietary history was obtained. SUBJECTS/SETTING: Subjects (n = 372) were participants in a study on maternal essential fatty acid status during pregnancy who did not have hypertension or any metabolic, cardiovascular, neurological, or renal disorder. Only pregnant white women with the intention to give birth in one of the three hospitals involved in the study were included. All three hospitals were located in the southern part of the Netherlands. STATISTICAL ANALYSES PERFORMED: The relation between maternal nutrition and fetal growth was evaluated using multiple regression analyses. RESULTS: Maternal intake of n-3 fatty acids plus arachidonic acid and of riboflavin were associated positively with fetal growth. A negative relation was observed between linoleic acid intake and fetal growth. APPLICATIONS/CONCLUSIONS: Our data suggest that the maternal diet during pregnancy is associated with fetal growth. Although this relationship ought to be more closely investigated, our results imply that much more attention should be paid to an adequate maternal diet during pregnancy, especially with respect to riboflavin and fatty acid intake.

Adolescent↗

Essential fatty acid status in plasma phospholipids of mother and neonate after multiple pregnancy.

During singleton pregnancy, maternal essential fatty acid (EFA) status decreases progressively. After multiple pregnancy it can be expected that the neonatal and maternal EFA status is even lower. To study whether the maternal EFA supply to the fetus is a limiting factor to the neonatal EFA status, we compared the plasma phospholipid EFA status of newborn multiplets (30 pairs of twins and 7 sets of triplets) with that of singletons (n = 89) at birth and that of their mothers at delivery. After correction for gestational age, a slightly lower EFA status was found in maternal and umbilical plasma from multiplets compared to singletons. No relation was found between the difference in birthweight of the smallest and the largest neonate of a set of multiplets and the difference in cord plasma EFA levels. Correlations between maternal and umbilical plasma EFA levels were comparable for multiple and singleton pregnancies. Therefore, adequate dietary intake is required to guarantee an optimal neonatal EFA status, especially during multiple pregnancy.

Birth Weight↗

Relation between birth order and the maternal and neonatal docosahexaenoic acid status.

OBJECTIVE: To investigate whether succeeding pregnancies will affect the maternal and neonatal docosahexaenoic acid (DHA, 22:6n-3) status. DESIGN: Cross-sectional study. SUBJECTS: Women who were pregnant for the 1st to 7th time and took part in a longitudinal study to investigate the essential fatty acid status of pregnant women and their infants. The total study population comprised 98 primigravidae (PG) and 146 multigravidae (MG). MAIN OUTCOME MEASURES: Fatty acid profiles of phospholipids isolated from maternal plasma samples collected during pregnancy and after delivery, and of umbilical plasma, vein and artery, obtained immediately after birth. RESULTS: The absolute (mg/L) and relative (% of total fatty acids) amounts of DHA in maternal plasma phospholipids (PL) were significantly lower in MG than in PG. In addition, a significant negative correlation was observed between gravida number and the DHA content in maternal plasma samples. The DHA deficiency index (22:5n-6/22;4n-6) was significantly higher and the DHA sufficiency index (22:6n-3/22:5n-6) was significantly lower in umbilical plasma of infants born of MG than in that of infants born of PG. The relative DHA content of umbilical artery and vein vessel walls was significantly lower in MG- than in PG-neonates and significant negative associations were observed between birth order and the relative amounts of DHA in cord tissues. CONCLUSIONS: These results indicate that the maternal DHA status becomes reduced after each following pregnancy, which may result in a lower neonatal DHA status. Whether or not this has also functional consequences needs to be investigated further.

Cross-Sectional Studies↗

Essential fatty acid status measured in umbilical vessel walls of infants born after a multiple pregnancy.

The essential fatty acid (EFA) status of full-term infants born after an uneventful, singleton pregnancy has been reported to be marginal. If this low EFA status is caused by a limiting maternal EFA supply, the higher total fetal EFA demand associated with a multiple pregnancy would result in an even lower EFA status of the infants born after a multiple pregnancy. Therefore, we compared the EFA status at birth of 30 pairs of twins, seven sets of triplets, and one set of quintuplets with that of 94 infants (51 preterm, 43 full-term) born after a singleton pregnancy. Phospholipid-associated EFA profiles of the umbilical vessel walls, considered a longer-term reflection of the fetal EFA status, were studied. After correction for gestational age at birth, levels of n-6 and n-3 EFAs were generally lower, while levels of EFA-deficiency indicating n-9 polyunsaturated fatty acids were significantly higher both in the draining umbilical arteries and the supplying veins of infants born after a multiple pregnancy. EFA profiles of twins and triplets were similar, but the average EFA status of the set of quintuplets was lower than that of twins and triplets. In conclusion, the observation that the EFA status of infants born after a multiple pregnancy is lower than that of infants born after a singleton pregnancy supports the view that the maternal EFA supply to the fetus is limiting. Considering the importance of EFAs and their longer chain derivatives for proper growth and development, this finding warrants further studies of the adequacy of the maternal EFA intake during pregnancy.

Adult↗